Ординатура / Офтальмология / Английские материалы / The Neurology of Eye Movements_Leigh, Zee_2006

tion (rotational or caloric) and especially with imbalance due to lesions.22'74 It has been postulated that, faced with a persisting vestibular imbalance (i.e., a false signal), the nervous system disables the neural integrator and the time constant of centripetal drift falls.37'74 In this way, centripetal drift due to a leaky neural integrator can be used to counteract the vestibular nystagmus in one field of gaze. The negative-exponential waveformsthat characterize a leaky neural integrator are difficult to discern in patients when a vestibular imbalance is also present.74 However, if the slow-phase velocity of a unidirectional nystagmus varies with orbital position, impaired integration can be inferred. Such waveforms have been identified following experimental lesions of the peripheral vestibular organ or nerve in monkeys.25

Vertical gaze-evoked nystagmus is caused by medications and by brain stem and cerebellar lesions that also disrupt horizontal gaze holding. Other causes of vertical gazeevoked nystagmus include bilateral internuclear ophthalmoplegia50 and lesions affecting the posterior commissure.66'67 Both the medial longitudinal fasciculus and the posterior commissure convey signals that encode vertical eye position.

Sometimes, disease involving the neural integrator causes nystagmus with exponentially increasing slow phases. This finding is indicative of an unstable rather than a leaky neural integrator. Nystagmus with increasing-velocitywaveforms is most commonly encountered in the horizontal plane as a feature of congenital nystagmus. It also occurs in some patients with cerebellar disease, who show horizontal or vertical nystagmus that is made worse by looking in the direction of the slow phases (see VIDEO: "Downbeat nystagmus").4'91 We have attempted to interpret this finding by the simple integrator model in Figure 5-6. Nystagmus with slow phases that variably increase or decrease in velocity and have a variable neutral point has been reported in blind individuals (see VIDEO: "Eye movements with complete blind- ness")51-52 and following experimental occipital lobectomy.92 In such cases, it seems that deprivation of visual or vestibular inputs can cause the neural integrator to be-

come uncalibrated, with a variable, inappropriate performance. Similar drifts of the eyes are reported following experimental cerebellectomy.71

Pathogencsis of Centripetal

Nystagmus and

Rebound Nystagmus

Persistent effort at maintaining eccentric gaze usually reduces the intensity of gazeevoked nystagmus and may actually cause a reversal of direction, so-called centripetal nystagmus (Display 10-7, Chap. 10).49 If the patient then returns the eyes to the central position, a transient nystagmus may be observed with slow phases occurring in the direction of former gaze; this is called rebound nystagmus (see VIDEO: "Gaze-evoked, rebound and downbeat nystagmus").41 Rebound nystagmus occurs in normal subjects after prolonged, eccentric gaze.78 In normals, rebound nystagmus partly reflects the development of a drift (velocity bias) to counter the centripetal drifts of the eyes; in addition, the time constant of the neural integrator may be shortened.34 Clinicians most frequently encounter rebound nystagmus in patients with cerebellar disease (Fig. 10-9),7-41 but it has been reported in monkeys with bilateral lesions restricted to the NPH and MVN.13 On the other hand, rebound nystagmus in one patient who had a choroid plexus papilloma involving the flocculus and nodulus disappeared when the vestibular nucleus was invaded by tumor.90

Since rebound nystagmus can occur following eccentric gaze holding in the dark,

occurs in patients who have impaired pursuit,7 so abnormalities of the pursuit system are unlikely to be primarily responsible for it. More likely, the generation of rebound nystagmus depends upon the ability to internally monitor eye movement signals (i.e., efference copy or proprioception) and activate compensatory eye drifts. Rebound nystagmus only occurred during the recovery phase following lesions of the NPH and MVN, indicating that some neural integra-

tor function may be necessary for its generation.13

SUMMARY

1.For normal conjugate eye movements, the ocular motoneurons carry a neural signal that contains velocity and position components. Such a signal is necessary to hold the eyes steady at an eccentric position in the orbit (see Fig. 1-3, Chap. 1). The po- sition-coded ocular motor signal is obtained from the velocity-coded signal by a process of mathematical integration. Electrophysiological evidence indicates that a common neural network integrates all conjugate eye movement commands; this network is called the neural integrator.

2.For horizontal, conjugate eye movements, the nucleus prepositus hypoglossi and medial vestibular nuclei are of prime importance for holding steady, eccentric gaze. Unilateral lesions of this NPH-MVN region cause partial, bilateral loss of gaze holding; bilateral lesions abolish the horizontal neural integrator. For vertical eye movements, midbrain structures, especially the interstitial nucleus of Cajal, contribute to neural integration. The vestibulocerebellum also contributes to the integration of ocular motor signals, and this role may depend on feedback of eye movement signals by the cell groups of the paramedian tracts. Thus, mathematical integration of ocular motor signals may be achieved by a network of interconnected neurons.

3.Inadequate neural integration causes a rapid decay in the eye-position signal and consequent negative exponential drift of the eyes back from an eccentric to a neutral position (see Fig. 5-3B). Clinically, this is manifest as gaze-evoked nystagmus. Such impaired integration is a common side effect of medications and is caused by disease affecting the vestibulocerebellum and brain stem. Deficient neural integration also impairs vestibular,

optokinetic, and pursuit eye movements. Vestibular lesions lead to a deficient neural integrator, in addition to causing a tonic vestibular imbalance. This combination of deficits can be seen in Alexander's law—nystagmus with a slow-phase velocity that increases when the eyes are brought to a position in the orbit in the direction of the quick phases.

4.The nervous system can partially compensate for deficient integrator function by programing oppositedirected, adaptive drifts of the eyes that are apparent as rebound nystagmus. If the nervous system is deprived of vision (blindness), the neural integrator loses its calibration and is unable to hold gaze steady.

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BRAIN STEM CONNECTIONS FOR HORIZONTAL

CONJUGATE MOVEMENTS Interpretation of the Effects of Discrete

Lesions on Pathways for Horizontal Gaze BRAIN STEM CONNECTIONS FOR

VERTICAL ANDTORSIONAL MOVEMENTS

CEREBELLAR INFLUENCES ON GAZE Contributions of the Vestibulocerebellum to

Gaze Control

Contributions of the Dorsal Vermis and Fastigial Nucleus to Gaze Control

THE CEREBRALHEMISPHERES AND VOLUNTARY CONTROLOF EYE MOVEMENTS

Approaches to Studying the Cerebral Control of Eye Movements in Humans

Contributions of Posterior Cortical Areas to

Gaze Control

Contributions of the Temporal Lobe to Gaze Control

Contributions of the Parietal Lobe to Gaze Control

Contributions of the Pulvinar to Gaze Control Contributions of the Frontal Lobe to Gaze

Control

Descending, Parallel Pathways that Control Voluntary Gaze

SUMMARY

This chapter provides an anatomic scheme for the synthesis of neural commands for conjugate eye movements. We present a hy-

pothesis to account for the way that neural signals for vestibular, optokinetic, saccadic, and pursuit eye movements and the gazeholding mechanism (neural integrator) project to ocular motoneurons. At the outset, the reader should realize that we draw on findings from studies of both humans and monkeys to forge our hypothesis. Although such an approach carries the risk of making inaccurate suppositions, it also enhances the opportunities for experimental tests.

Our approach is from the bottom up. First, we discuss the brain stem machinery responsible for all conjugate eye move- ments—reflex or voluntary. Second, we summarize the role of the cerebellum. Fi-

nally, we review the pathways responsible for voluntary eye movements. Although most of our account concerns anatomy, we will recapitulate important neurophysiologic points and summarize what is currently known about the neurotransmitters for these pathways. We will also outline the effects of certain well-defined lesions and lay out an anatomic basis for the topological diagnosis of clinical conditions that are discussed in Chapter 10.

BRAIN STEM CONNECTIONS FOR HORIZONTAL CONJUGATE MOVEMENTS

The tegmentum of the pons contains the neural machinery that ultimately controls

horizontal conjugate eye movements (Fig. 6-1). The most important structure is the abducens nucleus, which controls conjugate movements of both the ipsilateral lateral rectus and the contralateral medial rectus muscles (Display 6-1); thus it may be regarded as the horizontal gaze center. The abducens nucleus houses abducens motoneurons, which innervate the lateral rectus muscle, as well as abducens internuclear neurons, which project up the contralateral medial longitudinal fascicu-

lus (MLF) (Display 6-2) to contact medial

rectus motoneurons of the oculomotor nucleus (Fig. 6-1).$0,127 Thus, the axons of

the abducens nerve, together with those of the abducens internuclear neurons that course in the MLF, encode conjugate horizontal eye movements.157'261 Abducens motoneurons and internuclear neurons are partially intermingled but show some morphologic differences.192 Abducens motoneurons have no axon collaterals, but the internuclear neurons send collaterals

to the cell groups of the paramedian tracts (PMT cell groups), which lie in the midline of the brain stem and, in turn, project to the cerebellum.47'192 Abducens motoneurons and internuclear neurons are pharmacologically distinct: the motoneurons use acetylcholine, and the internuclear neurons use glutamate.53'194'304 Although both populations of neurons show qualitatively similar electrophysiologic properties, internuclear neurons show a lower sensitivity for eye position and a higher sensitivityfor eye velocity.96

How do signals for each functional class of eye movement reach the abducens nucleus? Figure 6-1 summarizes monosy-

naptic excitatory and inhibitory projections to the abducens nucleus and indicates neurotransmitters that have been postulated for these projections.194 Vestibular and optokinetic inputs reach the abducens nucleus from the vestibular nuclei; some of these axons pass through the ipsilateral abducens nucleus en route to the contralateral abducens nucleus.193 Excitatory saccadic commands originate from burst neurons that lie in the ipsilateral paramedian pontine reticular formation (PPRF) (Fig. 6-2; Display 6-3), rostral to the abducens nucleus.140'141'313 Excitatory burst neurons may be separated into two populations, projecting either to abducens

motoneurons or to internuclear neurons.i89a,354 Inhibitory saccadic commands

originate from burst neurons located contralaterally, in the paramedian reticular formation caudal to the abducens nucleus, at the pontomedullary junction.140'314 Inhibitory burst neurons are driven by monosynaptic projections from ipsilateral excitatory burst neurons (see Chap. 3). Pursuit signals are relayed from the cerebellum, in part via the vestibular nuclei.95'169 The output of the gaze-holding network (neural integrator) reaches the abducens nucleus from the nucleus prepositus hypoglossi (NPH) and adjacent medial vestibular nucleus (MVN).17>169 In addition, the abducens nucleus receives a projection from the contralateral medial rectus subdivision of the oculomotor complex (oculomotor internuclear neurons),

which contributes to the control of conjugate gaze.60'169

In addition to inputs via the MLF, medial rectus motoneurons receive direct projections from neurons in the ipsilateral

vestibular nucleus via the ascending tract of Deiters (see Fig. 2-3, Chap. 2),193'268

which runs lateral to the MLF and may play a role in adjusting the vestibular responses during near-viewing.573 Medial rectus motoneurons also receive inputs for vergence eye movements from neurons in the mesencephalic reticular formation,

which lie dorsolateral to the oculomotor nucleus.41'190

All the neurons that project to the abducens nucleus also send axon collaterals to a continuum of cell clusters that lie close to the MLF and other paramedian tracts in the caudal pons and medulla; these

have been called the cell groups of the paramedian tracts (PMT) (see Display 6-4 and Fig. 6-3).43'47 One of these cell groups lies at the rostral end of the abducens nucleus. The PMT cell groups, in turn, project to

the cerebellar flocculus, paraflocculus, and vermis of the cerebellum.39'43 In this way, the cerebellum may receive feedback about all motor signals flowing to the abducens nucleus. The possible role of the